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Nutritional Neurosciences

Folic Acid Supplementation Can Reduce the Endothelial Damage in Rat Brain Microvasculature Due to Hyperhomocysteinemia^1,2

Hwayoung Lee^*,, Ji-myung Kim^**, Ho Jin Kim^*, Insun Lee^** and Namsoo Chang^**,,3

^* Department of Anatomy, College of Medicine, ^** Department of Food and Nutritional Sciences, and Medical Research Center and Asia Food and Nutrition Research Institute, Ewha Womans University, Seoul, Republic of Korea

³To whom correspondence should be addressed. E-mail: nschang{at}ewha.ac.kr.

To evaluate the effects of dietary folic acid supplementation on the cerebral vascular damage induced by hyperhomocysteinemia, rats were fed a diet containing 3.0 g/kg homocystine for 2 wk and then either 3.0 g/kg homocystine or 3.0 g/kg homocystine plus 0.008 g/kg folic acid for 8 wk. Control rats consumed the AIN-93 Maintenance diet throughout the experiment. The cerebral expression of glucose transporter-1 was measured by Western blot analysis and cerebrovascular structural alterations were evaluated by electron microscopy. The homocystine diet significantly increased the plasma levels of homocysteine and TBARS and decreased the cerebral expression of glucose transporter-1 (GLUT-1) with a concomitant increase in the percentage of damaged cerebral vessels. The inclusion of dietary folic acid for 8 wk caused plasma homocysteine levels to be the same as in control rats and it significantly upregulated the cerebral expression of GLUT-1 that was significantly reduced by hyperhomocysteinemia. Folic acid supplementation also significantly decreased the incidence of damaged vessels due to hyperhomocysteinemia. These results and the electron microscopy findings suggested that folic acid supplementation might reduce the detrimental effects on the endothelium caused by experimentally induced hyperhomocysteinemia.

KEY WORDS: • brain • hyperhomocysteinemia • electron microscopy • folic acid • TBARS

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